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FDA Approves First Drug for Cancers with a High Tumor Mutational Burden

The US Food and Drug Administration (FDA) has expanded the approval of the immunotherapy drug pembrolizumab (Keytruda) to include any cancer with a high tumor mutational burden (TMB-H). The new approval is for adults and children with advanced TMB-H solid tumors that are still growing despite prior treatment, and for which there are no other good treatment options.

Tumor mutational burden (TMB) is a measure of the number of gene mutations (changes) inside the cancer cells, which can be determined by a lab test. Cells that have many gene mutations (a high TMB) might be more likely to be recognized as abnormal and attacked by the body’s immune system.

Keytruda is a type of drug known as an immune checkpoint inhibitor. It works by helping the immune system recognize cancer cells and attack them.

Keytruda was already approved for treating several types of cancer, including some types of lung, head and neck, stomach, liver, kidney, bladder, and skin cancers, as well as some types of lymphoma.

Keytruda was also previously approved for all advanced solid tumors with different types of gene changes – either high levels of microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). Cancer cells with MSI-H or dMMR have trouble repairing DNA damage. This can lead to them being very different from normal cells, which can make them more visible to the body’s immune system.

The new FDA approval is based on a clinical trial in which patients’ tumors were tested for TMB. Of the 790 patients tested, 102 (13%) had cancers that were TMB-H. The most common TMB-H cancers in the study were small cell lung cancer, cervical cancer, endometrial cancer, anal cancer, and vulvar cancer. Among the 102 patients with TMB-H cancers, the cancer responded (shrank or disappeared) in 29% during treatment with this drug. The average response time was 30 months, with half of the responses lasting for at least two years.

Keytruda was approved for the new indication using accelerated approval and priority review, programs the FDA can use to speed up the availability of drugs to treat serious diseases. Under accelerated approval, the company that makes the drug still needs to submit additional clinical information after approval to demonstrate its benefit. Priority review means the FDA tries to make a decision within 6 months instead of the usual 10 months.

Keytruda is given as an infusion into a vein, typically once every 3 or 6 weeks.

The most common side effects of this drug are fatigue, fever, cough, shortness of breath, nausea, itchy skin, rash, decreased appetite, constipation, muscle or joint pain, and diarrhea. Less common but more serious side effects can occur when the drug causes the immune system to attack normal cells in the body. This can lead to serious problems in the lungs, colon, hormone-making glands, liver, skin, or other organs.

Keytruda is manufactured by Merck & Co.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

US Food and Drug Administration (FDA). FDA approves pembrolizumab for adults and children with TMB-H solid tumors. Accessed at on June 18, 2020.